A double-blind, randomized, placebo controlled, parallel group, multi-center, phase III trial of ofatumumab investigating clinical efficacy In adult patients wlth active rheumatoid arthritis who had an inadequate response to TNF-a antagonist therapy
- Conditions
- -M139M139
- Registration Number
- PER-102-07
- Lead Sponsor
- GlaxoSmithKline,
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Complete
- Sex
- Not specified
- Target Recruitment
- 31
• Age 18 years
• Diagnosis of rheumatoid arthritis according to the American College of Rheumatology (classification ACR1987) of at least six months from the time of diagnosis to selection
• Active disease at the time of selection, defined by: - 8 swollen joints (over 66 joints evaluated) and 8 painful joints (over 68 joints evaluated) and C reactive protein (POR) 1.0 mg / dl or erythrocyte sedimentation rate (VES) 22 mm / hour (with the Becton Dickinson Seditainer) and DAS28 3.2 (based on the VES)
• FUND class of ARI, II or III *
• Inadequate response to previous or ongoing treatment with a TNF-a antagonist after treatment with infliximab (^ 3 mg / kg, at least 4 infusions) or with adalimumab (40 mg week per half for ^ 3 months), or therapy with etanercept (25mg twice a week or 50 mg once a week for ^ 3 months) defined as: 1. Inadequate efficacy, according to the investigator´s criteria and / or 2. Intolerance, defined as one or more side effects after administration of imo of TNF-cx antagonists at the doses listed above, which reasonably leads to discontinuation of treatment with the TNF-a antagonist
• Treatment with methotrexate (MTX), 7.5-25 mg / week, for at least 12 weeks and in a stable dose for at least 4 weeks before Visit 2. MTX doses of only 7.5 are allowed mg per week for subjects who may be intolerant at higher doses
• After receiving verbal and written information about the study, the subject must provide his / her signed informed consent before carrying out any activity related to the study, including the period of pharmacological rest of other medicines France: In France, a subject will be eligible for inclusion in the study only if you are a member or beneficiary of a social security system.
• Subjects with a history of rheumatic autoimmune disease other than RA (except secondary Sjogren´s syndrome, significant secondary systemic involvement AR (vasculitis, pulmonary fibrosis or Felty´s syndrome)
• Previous exposure to biological antirheumatic therapies that cause cellular depletion, including experimental compounds (eg, anti- CDlla, apti-CD19, anti-CD20, anti-CD22, anti-BLyS / BAFF, anti-CD3, anti-CD4, anti-CD5, CAMPATH)
• 411: Exposure to etanercept for 4 weeks, infliximab or adalimumab for 8 weeks or abatacept for 12 weeks before Visit 2
• Subjects who received any of the following treatments in the 4 weeks prior to the
• Visit 2; - Antineoplastic treatments (eg alkylating agents, antimetabolites, purine analogues, monoclonal antibodies) - Glucocorticoids, unless administered in doses equivalent to 10 mg (prednisolone / day - IM or IV intraarticular corticosteroids - Vaccination with live / attenuated viruses - Hydroxychloroquine - Cyclosporine - Azathioprine - Penicillamine
• Exposure to sulfasalazine in the 6 weeks prior to Visit 2
• Exposure to leflunomide in the 12 weeks prior to Visit 2, except that the subject has completed oral treatment with cholestyramine for drug rest according to locally accepted clinical practices
• Exposure to treatments with gold salts 12 weeks before Visit 2
• Exposure to immunoglobulins IV 24 weeks before Visit 2
• Past or current malignant melanoma
• 10) Past or current malignancy except: - Stage 1B or less cervical carcinoma - Non-invasive basal cell and squamous cell carcinoma - Other cancers with complete remission duration> 5 years
• Chronic or active infectious disease in progress that requires systemic treatment, such as the following, but not limited to: chronic kidney infection, chronic chest infection with bronchiectasis, tuberculosis and active hepatitis B and C
• Clinically significant heart disease, including instable angina, acute myocardial infarction in the six months prior to selection, congestive heart failure, known QT abnormalities, and arrhythmias requiring treatment, with the exception of extrasystoles or minor conduction abnormalities.
• Significant, concurrent, uncontrolled clinical conditions, including, but not limited to: renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral psychiatric diseases or evidence of demyelinating disease
• History of significant cerebrovascular disease
• Known positivity for HIV
• Laboratory values of the selection (according to the central laboratory); - Hemoglobin <5.6 mmol / 1 (9.0 g / dl) - Neutrophils <2 x 10 9 / l - Platelets <100 xx 10 9 / l - serum IgG 3.0 times the upper limit of normal - S-AST > 1.5 times the upper limit of normal - S-ALP > 2 times the upper limit of normal - S-creatinine > 133 pmol / l (1.5 mg / dl)
• Positive serology for hepatitis B (HB) defined as: - Positive test for HBsAg and / or - Positive test for anti-HBc and anti-HBs. Subjects with documented vaccination against Hepatitis B (primary and secondary immunization plus reinforcement) will be considered negative
• Positive PCR in plasma / leukocytes for JC Virus (JCV) virus (any compartment)
• Known hypersensitivity to medicinal product components in research
• Subjects who have received treatment with any other non-commercialized drug substance or experimental treatment in the 4 wee
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method